7-116576975-T-C

Position:

• chr7-116576975-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_165032.1(COMETT):​n.391-5745A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,158 control chromosomes in the GnomAD database, including 48,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48886 hom., cov: 33)
• Consequence: COMETT NR_165032.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

Genes affected

COMETT (HGNC:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COMETT	NR_165032.1	n.391-5745A>G		intron_variant, non_coding_transcript_variant
COMETT	NR_120506.2	n.204-3231A>G		intron_variant, non_coding_transcript_variant
COMETT	NR_165033.1	n.391-3231A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COMETT	ENST00000650435.1	n.320-3231A>G		intron_variant, non_coding_transcript_variant
COMETT	ENST00000441991.1	n.86-3231A>G		intron_variant, non_coding_transcript_variant		3
COMETT	ENST00000458082.1	n.367-3231A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121781 AN: 152040 Hom.: 48848 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.801 AC: 121880 AN: 152158 Hom.: 48886 Cov.: 33 AF XY: 0.805 AC XY: 59853 AN XY: 74396

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.796

Alfa AF: 0.810 Hom.: 95118

Bravo AF: 0.802

Asia WGS AF: 0.865 AC: 3009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7795356; hg19: chr7-116217029; COSMIC: COSV71451730;